Inhibition of Human Colorectal Cancer by a Natural Product 7-Acetylhorminone and Interactions with BSA/HSA: Multispectral Analysis and In Silico and In Vitro Studies.

We have semi-synthesized a natural product 7-acetylhorminone from crude extract of Premna obtusifolia (Indian headache tree), which is active against colorectal cancer after probation through computational screening methods as it passed through the set parameters of pharmacokinetics (most important nonblood-brain barrier permeant) and drug likeliness (e.g., Lipinski's, Ghose's, Veber's rule) which most other phytoconstituents failed to pass combined with docking with EGFR protein which is highly upregulated in the colorectal carcinoma cell. The structure of 7-acetylhorminone was confirmed by single crystal X-ray diffraction studies and 1H NMR, 13C NMR, and COSY studies. To validate the theoretical studies, first, in vitro experiments were carried out against human colorectal carcinoma cell lines (HCT116) which revealed the potent cytotoxic efficacy of 7-acetylhorminone and verified preliminary investigation. Second, the drugability of 7-acetylhorminone interaction with serum albumin proteins (HSA and BSA) is evaluated both theoretically and experimentally via steady-state fluorescence spectroscopic studies, circular dichroism, isothermal titration calorimetry, and molecular docking. In summary, this study reveals the applicability of 7-acetylhorminone as a potent drug candidate or as a combinatorial drug against colorectal cancer.

Thermally processed Ni-and Co-struvites as functional materials for proton conductivity.

Here, we describe how to synthesise proton-conductive transition metal phosphates (TMPs) by direct thermal processing of precursor M-struvites, NH4MPO4·6H2O, with M = Ni2+, Co2+. In the as-derived TMP phases their thermal history and bulk proton conductivity were linked with the structural information about the metal coordination, phosphate groups, and volatile compounds. These aspects were investigated with vibrational and synchrotron-based spectroscopic methods (FT-IR, FT-RS, XAS). We elucidated the structures of amorphous and crystalline Ni- and Co phosphate phases in association with different coordination changes and distortion degrees of the metal polyhedra as they developed upon heating. Ni-struvite transformed to a stable amorphous phase over a broad range of temperatures (90 °C < T < 600 °C), in which it remained in an octahedral coordination environment, but the degree of distortion changed with T. In contrast, heating of Co-struvite led to several successive crystalline phases with only unstable transitional and short-lived amorphous components. Among the as-occurring phases, a highly functional layered M-dittmarite NH4MPO4·H2O obtained at low temperatures (T < 200 °C) demonstrated high proton conductivity values of 4.2 × 10-5 S cm-1 for Ni-dittmarite and Co-dittmarite > 10-4 S cm-1 at room temperature. Even at low humidity, these values are comparable with those found for Nafion, MOFs, some perovskites or composite materials. Coprecipitation of phosphates and transition metal cations in the form of struvite is potentially a viable method to extract these elements from wastewater. Thus, we propose that recycled M-struvites could be potentially further directly upcycled into crystalline and amorphous TMPs useful for electrochemical applications.

Synthesis and In Situ Monitoring of Mechanochemical Preparation of Highly Proton Conductive Hydrogen-Bonded Metal Phosphonates.

Crystalline porous materials are recognized as promising proton conductors for the proton exchange membrane (PEM) in fuel cell technology owing to their tunable framework structure. However, it is still a challenging bulk synthesis for real-world applications of these materials. Herein, we report the mechanochemical gram-scale synthesis of two isostructural metal hydrogen-bonded organic frameworks (MHOFs) of Co(II) and Ni(II) based on 1-hydroxyethylidenediphosphonic acid (HEDPH4) with 2,2'-bipyridine (2,2'-bipy): Co(HEDPH3)2(2,2'-bipy)·H2O (1) and Ni(HEDPH3)2(2,2'-bipy)·H2O (2). In situ monitoring of the mechanochemical synthesis using different synchrotron-based techniques revealed a one-step mechanism - the starting materials are directly converted to the product. With the existence of extensive hydrogen bonds with amphiprotic uncoordinated phosphonate hydroxyl and oxygen atoms, both frameworks exhibited proton conduction in the range of 10-4 S cm-1 at room temperature under humid conditions. This study demonstrates the potential of green mechanosynthesis for bulk material preparation of framework-based solid-state proton conductors.

An atomistic mechanism for elasto-plastic bending in molecular crystals.

Mechanically flexible single crystals of molecular materials offer potential for a multitude of new directions in advanced materials design. Before the full potential of such materials can be exploited, insight into their mechanisms of action must be better understood. Such insight can be only obtained through synergistic use of advanced experimentation and simulation. We herein report the first detailed mechanistic study of elasto-plastic flexibility in a molecular solid. An atomistic origin for this mechanical behaviour is proposed through a combination of atomic force microscopy, µ-focus synchrotron X-ray diffraction, Raman spectroscopy, ab initio simulation, and computed elastic tensors. Our findings suggest that elastic and plastic bending are intimately linked and result from extensions of the same molecular deformations. The proposed mechanism bridges the gap between contested mechanisms, suggesting its applicability as a general mechanism for elastic and plastic bending in organic molecular crystals.

Mechanochemical Synthesis of Phosphonate-Based Proton Conducting Metal-Organic Frameworks.

Water-stable metal-organic frameworks (MOFs) with proton-conducting behavior have attracted great attention as promising materials for proton-exchange membrane fuel cells. Herein, we report the mechanochemical gram-scale synthesis of three new mixed-ligand phosphonate-based MOFs, {Co(H2PhDPA)(4,4'-bipy)(H2O)·2H2O}n (BAM-1), {Fe(H2PhDPA)(4,4'-bipy) (H2O)·2H2O}n (BAM-2), and {Cu(H2PhDPA)(dpe)2(H2O)2·2H2O}n (BAM-3) [where H2PhDPA = phenylene diphosphonate, 4,4'-bipy = 4,4'-bipyridine, and dpe = 1,2-di(4-pyridyl)ethylene]. Single-crystal X-ray diffraction measurements revealed that BAM-1 and BAM-2 are isostructural and possess a three-dimensional (3D) network structure comprising one-dimensional (1D) channels filled with guest water molecules. Instead, BAM-3 displays a 1D network structure extended into a 3D supramolecular structure through hydrogen-bonding and π-π interactions. In all three structures, guest water molecules are interconnected with the uncoordinated acidic hydroxyl groups of the phosphonate moieties and coordinated water molecules by means of extended hydrogen-bonding interactions. BAM-1 and BAM-2 showed a gradual increase in proton conductivity with increasing temperature and reached 4.9 × 10-5 and 4.4 × 10-5 S cm-1 at 90 °C and 98% relative humidity (RH). The highest proton conductivity recorded for BAM-3 was 1.4 × 10-5 S cm-1 at 50 °C and 98% RH. Upon further heating, BAM-3 undergoes dehydration followed by a phase transition to another crystalline form which largely affects its performance. All compounds exhibited a proton hopping (Grotthuss model) mechanism, as suggested by their low activation energy.

Adaptable Optical Microwaveguides From Mechanically Flexible Crystalline Materials.

Flexible organic crystals (elastic and plastic) are important materials for optical waveguides, tunable optoelectronic devices, and photonic integrated circuits. Here, we present highly elastic organic crystals of a Schiff base, 1-((E)-(2,5-dichlorophenylimino)methyl)naphthalen-2-ol (1), and an azine molecule, 2,4-dibromo-6-((E)-((E)-(2,6-dichlorobenzylidene)hydrazono)methyl)phenol (2). These microcrystals are highly flexible under external mechanical force, both in the macroscopic and the microscopic regimes. The mechanical flexibility of these crystals arises as a result of weak and dispersive C-H⋅⋅⋅Cl, Cl⋅⋅⋅Cl, Br⋅⋅⋅Br, and π⋅⋅⋅π stacking interactions. Singly and doubly-bent geometries were achieved from their straight shape by a micromechanical approach using the AFM cantilever tip. Crystals of molecules 1 and 2 display a bright-green and red fluorescence (FL), respectively, and selective reabsorption of a part of their FL band. Crystals 1 and 2 exhibit optical-path-dependent low loss emissions at the termini of crystal in their straight and even in extremely bent geometries. Interestingly, the excitation position-dependent optical modes appear in both linear and bent waveguides of crystals 1 and 2, confirming their light-trapping ability.

Bioinformatics and Network Pharmacology of the First Crystal Structured Clerodin: Anticancer and Antioxidant Potential against Human Breast Carcinoma Cell.

Clerodin was isolated from the medicinal plant Clerodendrum infortunatum, and CSD search showed the first crystal structure of clerodin by a single-crystal X-ray diffraction study. We checked its binding potential with target proteins by docking and conducted network pharmacology analysis, ADMET analysis, in silico pathway analysis, normal mode analysis (NMA), and cytotoxic activity studies to evaluate clerodin as a potential anticancer agent. The cell viability studies of clerodin on the human breast carcinoma cell line (MCF-7) showed toxicity on MCF-7 cells but no toxicity toward normal human lymphocyte cells (HLCs). The anticancer mechanism of clerodin was validated by its enhanced capacity to produce intracellular reactive oxygen species (ROS) and to lower the reduced glutathione content in MCF-7 cells.

High-pressure reversibility in a plastically flexible coordination polymer crystal.

Single crystals which exhibit mechanical flexibility are promising materials for advanced technological applications. Before such materials can be used, a detailed understanding of the mechanisms of bending is needed. Using single crystal X-ray diffraction and microfocus Raman spectroscopy, we study in atomic detail the high-pressure response of the plastically flexible coordination polymer [Zn(µ-Cl)2(3,5-dichloropyridine)2]n (1). Contradictory to three-point bending, quasi-hydrostatic compression of (1) is completely reversible, even following compression to over 9 GPa. A structural phase transition is observed at ca. 5 GPa. DFT calculations show this transition to result from the pressure-induced softening of low-frequency vibrations. This phase transition is not observed during three-point-bending. Microfocus synchrotron X-ray diffraction revealed that bending yields significant mosaicity, as opposed to compression. Hence, our studies indicate of overall disparate mechanical responses of bulk flexibility and quasi-hydrostatic compression within the same crystal lattice. We suspect this to be a general feature of plastically bendable materials.

Mechanical-Bending-Induced Fluorescence Enhancement in Plastically Flexible Crystals of a GFP Chromophore Analogue.

Single crystals of optoelectronic materials that respond to external stimuli, such as mechanical, light, or heat, are immensely attractive for next generation smart materials. Here we report single crystals of a green fluorescent protein (GFP) chromophore analogue with irreversible mechanical bending and associated unusual enhancement of the fluorescence, which is attributed to the strained molecular packing in the perturbed region. Soft crystalline materials with such fluorescence intensity modulations occurring in response to mechanical stimuli under ambient pressure conditions will have potential implications for the design of technologically relevant tunable fluorescent materials.

Metal-like Ductility in Organic Plastic Crystals: Role of Molecular Shape and Dihydrogen Bonding Interactions in Aminoboranes.

Ductility is a common phenomenon in many metals but is difficult to achieve in molecular crystals. Organic crystals bend plastically on one or two face-specific directions but fracture when stressed in any other arbitrary directions. An exceptional metal-like ductility and malleability in the isomorphous crystals of two globular molecules, BH3 NMe3 and BF3 NMe3 , is reported, with characteristic tensile stretching, compression, twisting, and thinning. The mechanically deformed samples, which transition to lower symmetry phases, retain good long-range order amenable to structure determination by single-crystal X-ray diffraction. Molecules in these high-symmetry crystals interact through electrostatic forces (B- -N+ ) to form columnar structures with multiple slip planes and weak dispersive forces between columns. On the other hand, the limited number of facile slip planes and strong dihydrogen bonding in BH3 NHMe2 negates ductility. Our study has implications for the design of soft ferroelectrics, solid electrolytes, barocalorics, and soft robotics.

A Mechanistic Perspective on Plastically Flexible Coordination Polymers.

Mechanical flexibility in single crystals of covalently bound materials is a fascinating and poorly understood phenomenon. We present here the first example of a plastically flexible one-dimensional (1D) coordination polymer. The compound [Zn(µ-Cl)2 (3,5-dichloropyridine)2 ]n is flexible over two crystallographic faces. Remarkably, the single crystal remains intact when bent to 180°. A combination of microscopy, diffraction, and spectroscopic studies have been used to probe the structural response of the crystal lattice to mechanical bending. Deformation of the covalent polymer chains does not appear to be responsible for the observed macroscopic bending. Instead, our results suggest that mechanical bending occurs by displacement of the coordination polymer chains. Based on experimental and theoretical evidence, we propose a new model for mechanical flexibility in 1D coordination polymers. Moreover, our calculations propose a cause of the different mechanical properties of this compound and a structurally similar elastic material.

A reversible photochemical solid-state transformation in an interpenetrated 3D metal-organic framework with mechanical softness.

We synthesized a two-fold interpenetrated 3D MOF with two crystallographically distinct C[double bond, length as m-dash]C bonds, which undergoes [2+2] photo-cycloaddition and thermal reversible reaction, in a single-crystal-to-single-crystal (SCSC) manner. The softer nature and comparable mechanical properties of the crystals of the parent and cyclized MOFs revealed by nanoindentation allowed rationalizing their structural softness and SCSC transformation behaviour.

New Set of Multicomponent Crystals as Efficient Heterogeneous Catalysts for the Synthesis of Cyclic Carbonates.

Three new multicomponent crystals 1a-1c of Zn(II), Mn(II), and Co(II), respectively, were synthesized by the reaction of 2,6-bis(hydroxymethyl)pyridine, the respective metal salts, and sodium benzoate in a 1:1:2 ratio. One component of these multicomponent crystals 1a-1c is the dicationic 2,6-bis(hydroxymethyl)pyridine metal complex and the other component is the dianionic tetrabenzoate complex of the same metal. The complexes were fully characterized by single-crystal X-ray structure determination. The X-ray structure of these compounds 1a-1c reveals the formation of 1D supramolecular chain parallel to the crystallographic b axis via H-bonding interactions between the dicationic and dianionic parts of the respective compound. The Mn(II) (1b) and Co(II) (1c) complexes show antiferromagnetic coupling between the two associated metal centers via the H-bonding interaction pathway. All the three compounds 1a-1c were tested as heterogeneous catalytic systems for the successful conversion of epoxides to cyclic carbonates in solvent-free condition under approximately 10 bar of pressure of CO2 and temperature ranging between 60 and 80 °C along with tetrabutyl ammonium bromide acting as a cocatalyst. All the three compounds 1a-1c were found to have turnover number more than 1000 for the respective epoxides except for the conversion of cyclohexene oxide to cyclohexene carbonate.

Mechanically interlocked architecture aids an ultra-stiff and ultra-hard elastically bendable cocrystal.

Molecular crystals are not known to be as stiff as metals, composites and ceramics. Here we report an exceptional mechanical stiffness and high hardness in a known elastically bendable organic cocrystal [caffeine (CAF), 4-chloro-3-nitrobenzoic acid (CNB) and methanol (1:1:1)] which is comparable to certain low-density metals. Spatially resolved atomic level studies reveal that the mechanically interlocked weak hydrogen bond networks which are separated by dispersive interactions give rise to these mechanical properties. Upon bending, the crystals significantly conserve the overall energy by efficient redistribution of stress while perturbations in hydrogen bonds are compensated by strengthened π-stacking. Furthermore we report a remarkable stiffening and hardening in the elastically bent crystal. Hence, mechanically interlocked architectures provide an unexplored route to reach new mechanical limits and adaptability in organic crystals. This proof of concept inspires the design of light-weight, stiff crystalline organics with potential to rival certain inorganics, which currently seem inconceivable.

Polarity-Induced Excited-State Intramolecular Proton Transfer (ESIPT) in a Pair of Supramolecular Isomeric Multifunctional Dynamic Metal-Organic Frameworks.

A pair of supramolecular isomers of CdII -based MOF have been synthesized by utilizing a flexible N,N'-donor linker and a dicarboxylate with ESIPT (excited-state intramolecular proton transfer) fluorophore by varying the reaction media. One of the MOFs has a 3D four-fold interpenetrating framework with guest solvent in the structure that undergoes a solvent-dependent crystalline-to-crystalline structural transformation, which has been extensively studied by powder XRD and IR spectroscopy. The other MOF is structurally rigid in nature and has a two-fold interpenetrating structure without any guest molecules. Both the compounds show moderate CO2 adsorption and one of them, the MOF with the four-fold interpenetrating structure, also shows moderately high H2 adsorption. Furthermore, both the compounds show interesting luminescence behavior. In the solid state, the two compounds show single-peak spectra, whereas upon suspension of these compounds in polar solvents, the maxima split into two peaks with a large Stokes shift. On the other hand, in nonpolar solvents, only one emission maximum is observed. This solvatochromic dual-emission phenomenon is due to ESIPT, which has been extensively studied.

Eye-Catching Dual-Fluorescent Dynamic Metal-Organic Framework Senses Traces of Water: Experimental Findings and Theoretical Correlation.

A guest-dependent dynamic fivefold interpenetrated 3D porous metal-organic framework (MOF) of ZnII ions has been synthesized that exhibits selective carbon dioxide adsorption. Furthermore, the MOF shows excellent luminescence behavior, which is supported by a systematic study on the guest-responsive multicolor emission of a suspension of the MOF. The dual-emission behavior arises from the excited-state intramolecular proton transfer (ESIPT), and the compound also shows remarkable potential to detect traces of water in various organic solvents. The experimental observations were also painstakingly authenticated by using time-dependent density-functional-theory (DFT) calculations.

Tuned synthesis of two coordination polymers of Cd(II) using substituted bent 3-pyridyl linker and succinate: structures and their applications in anion exchange and sorption properties.

Two new Cd(II) coordination polymers, namely [Cd(3-bpdh)2(ClO4)2]n (1) and {[Cd(3-bpdh)(suc)(H2O)]·3(H2O)}n (2), have been synthesized using a substituted bent N,N'-donor ligand 2,5-bis-(3-pyridyl)-3,4-diaza-2,4-hexadiene (3-bpdh) and aliphatic dicarboxylate disodium succinate (suc) with Cd(II) perchlorate salts at room temperature by a slow diffusion technique for the exploration of our previous reported work. Both the structures were determined by single-crystal X-ray diffraction analysis and also by other physicochemical methods. Structure analysis revealed that complex 1 is a 1D chain structure containing coordinated perchlorate with a metal centre, and complex 2 shows a porous 3D framework with encapsulation of lattice water molecules into the void along the crystallographic a-axis. The PXRD study shows the bulk purity of both the complexes and TGA analysis of 2 exhibits that the structure is thermally stable up to 250 °C. Complex 1 shows a nice anion exchange property with replacement of weakly coordinated perchlorate with the inclusion of new anions; and the anion exchanged solids were characterised by FT-IR, PXRD and photoluminescence properties. The desolvated framework of 2 exhibits sorption of CO2 and water vapor and surface adsorption of N2 corroborating with the nature of the pore environment present in 2. The photoluminescence study has been also done for both complexes in the solid state which exhibits ligand based emissions at room temperature.

Cd(II) based metal-organic framework behaving as a Schottky barrier diode.

A metal-organic framework (MOF) of cadmium(ii) is reported here which is the first example of an experimentally achieved MOF based electronic device, and in the present case it is a Schottky diode.

Porous coordination polymers based on functionalized Schiff base linkers: enhanced CO2 uptake by pore surface modification.

We report the synthesis, structural characterization and adsorption properties of three new porous coordination polymers {[Cu(Meazpy)0.5(glut)](H2O)}n (2), {[Zn(azpy)0.5(terep)](H2O)}n (3), and {[Zn(Meazpy)0.5(terep)]}n (4) [glut = glutarate, terep = terephthalate, azpy = N,N'-bis-(pyridin-4-ylmethylene)hydrazine and Meazpy = N,N'-bis-(1-pyridin-4-ylethylidene)hydrazine] composed of mixed linkers systems. Structure determination reveals that all three compounds have three-dimensional (3D) coordination frameworks bridged by dicarboxylates and Schiff base linkers. In all cases 2D dicarboxylate layers are supported by paddle-wheel M2(CO2)4 SBUs extended in three dimensions by designed Schiff base linkers. Compound 1, which has been reported in a paper earlier by our group, is a robust porous three-dimensional (3D) framework whose pore surface was found to be decorated with the -CH=N- groups of a linear Schiff base (azpy) and it showed reversible single-crystal-to-single-crystal transformation and selective CO2 uptake. By using another linear Schiff base linker Meazpy, we have synthesized compound 2 which is isostructural with 1, having an additional methyl group pointing towards the pore. Like 1 it also shows a reversible single-crystal-to-single-crystal transformation upon dehydration and rehydration. The dehydrated framework of 2 exhibits 50% enhanced CO2 uptake compared to 1. This has been achieved by the pore surface modification effected upon changing the pillar backbone from a -CH=N- to -CMe=N- group. It also adsorbs water vapour at 298 K. In the case of the two isostructural 3D MOFs 3and 4, the use of a rigid carboxylate (terephthalate) linker arrested porosity by three-fold interpenetration. We showed that the use of aliphatic dicarboxylate (glutarate) results in a non-interpenetrated framework rather than the common interpenetrated framework with aromatic dicarboxylates in mixed ligand systems.